The Korean Patent Unexamined Publication Nos. 2003-0097706 and 2004-0066639 disclose that tetrafluorobenzyl derivatives are therapeutically effective in the prevention and treatment of acute and chronic neurodegenerative diseases and can effectively be used to prevent and treat chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease; seizure-inducing brain disease such as epilepsy; and ischemic brain disease such as stroke.
The process for preparing tetrafluorobenzyl-5-aminosalicylic acid derivatives is described in the Korean Patent Unexamined Patent No. 2003-0097706, and is illustrated in the following reaction scheme II.

Wherein, R1, R2 and R3 are hydrogen or halogen, respectively; R4 is hydroxy, alkyl, alkoxy, halogen, alkoxy substituted with halogen, alkanoyloxy or nitro, and R5 is carboxylic acid or ester of carboxylic acid substituted with C1-C4 alkyl, carboxyamide, sulfonic acid, halogen or nitro.
Reaction scheme II shows the process for preparing tetrafluorobenzyl-5-aminosalicylic acid derivatives. First, a nitrobenzene compound is hydrogenated, and the resulting aniline compound is reacted with tetrafluorobenzyl bromide compound in the presence of triethylamine and dimethylformimide resulting in the production of the desired tetrafluorobenzyl-5-aminosalicylic acid derivative.
The process, however, also results in the formation of a dimer (Chemical Formula III) in quantities greater than 1% of the total product. The dimmer is formed as a result of the side-reaction between the starting material, tetrafluorobenzyl bromide compound, and the secondary amine group of a tetrafluorobenzyl-5-aminosalicylic acid derivative. The dimer is not easily removed by general re-crystallization methods, and a more complex purification process is required in order to stay under the impurity guideline of 0.1%. This reaction scheme is therefore inadequate for industrial application. It produces a reduced yield of the desired compound, and thereby increases manufacturing costs.

Wherein, R1, R2 and R3 may, independently of one another, be hydrogen or halogen.
Furthermore, the Korean Patent Unexamined Patent No. 2003-0097706 fails to describe the salt compounds of tetrafluorobenzyl-5-aminosalicylic acid derivative in more detail. Thus, another formulation research of the aforementioned compound in terms of stability is required.
Through intensive and thorough research, the inventors have found that dimer formation in the manufacturing of tetrafluorobenzyl-5-aminosalicylic acid derivative may be avoided by using a tetrafluorobenzilidine-5-aminosalicylic acid derivative as an intermediate. As well, the stability of the desired compound was improved by preparing the salt compound using alkali metals, thus leading to this invention.